Aptivus (tipranavir) / Boehringer Ingelheim - LARVOL DELTA

QSAR-Based Drug Repurposing and RNA-Seq Metabolic Networks Highlight Treatment Opportunities for Hepatocellular Carcinoma Through Pyrimidine Starvation. (PubMed, Cancers (Basel)) - "For DHODH, the drugs Oteseconazole, Tipranavir, and Lusutrombopag were identified as potential inhibitors. For TYMS, the drugs Tadalafil, Dabigatran, Baloxavir Marboxil, and Candesartan Cilexetil showed promise as inhibitors. Overall, this study suggests in vitro testing of the identified drugs to assess their capabilities in inducing pyrimidine starvation on HCC."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • TYMS

Total Synthesis of Tipranavir Based on Iridium-Catalyzed Asymmetric Allylic Substitution of Dihydropyranone. (PubMed, Org Lett) - "High yield and diastereoselectivity (>20:1), as well as excellent enantioselectivity (99% ee), were obtained for the key intermediate through direct asymmetric alkylation reaction of dihydropyranone with allylic tert-butyl carbonate. Anti-AIDS drug of tipranavir was finally accomplished in 8 steps and 6 pots starting from commercially available 1-phenyl-3-hexanone in 20.7% overall yield with 99% ee and >20:1 dr."

Journal • Human Immunodeficiency Virus • Infectious Disease

Pharmacokinetics of Antiretroviral Drugs in Older People Living with HIV, Part II: Drugs Licensed Before 2005. (PubMed, Clin Pharmacokinet) - "Exposure to 3TC, TDF, FTC, ATV, LPV, and RTV increases with age, while exposure to ABC and EFV appears to be unaffected. Despite the large quantity of data on PK in young adults, there is still a gap in knowledge about the effects of aging on the PK of these ARVs."

Journal • PK/PD data • Review • Human Immunodeficiency Virus • Infectious Disease

Pretreatment drug resistance among people living with HIV from 2018 to 2022 in Guangzhou, China. (PubMed, J Med Virol) - "Abacavir (0.8%) resistance was the most common in NRTI, followed by resistance to emtricitabine (0.6%), lamivudine (0.6%), and tenofovir disoproxil fumarate (0.3%). In NNRTI, nevirapine (3.7%) resistance was the most common, followed by efavirenz (3.5%) and rilpivirine (3.4%). Among PI, resistance to tipranavir (0.8%), nelfinavir (0.6%), fosamprenavir (0.2%) and lopinavir (0.1%) was most frequent...The overall prevalence of PDR in Guangzhou was moderate, with relatively severe NNRTI resistance. Therefore, it remains crucial to continue monitoring PDR among newly diagnosed HIV-infected individuals."

Journal • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation

Quantitative Prediction of Human Immunodeficiency Virus Drug Resistance. (PubMed, Viruses) - "The models built demonstrate reasonable performances for eight out of nine (R2 varied from 0.828 to 0.909) protease inhibitors, while R2 for predicting tipranavir fold ratio was lower (R2 was 0.642). We believe that the developed approach can be applied to evaluate drug resistance of molecular targets of other viruses where appropriate experimental data are available."

Journal • Human Immunodeficiency Virus • Infectious Disease

Dengue virus: pathogenesis and potential small molecule antivirals. (PubMed, Biosci Rep) - "Several potential small-molecule inhibitors like efavirenz, tipranavir and dasabuvir have been tested against envelope and non-structural proteins of DENV, and are in clinical trials around the world. 7D inhibited all 4 serotypes of DENV in vitro and specifically DENV2 infection in two different mice models.  Although the development of dengue vaccines remains a high priority, antibody cross reactivity among the serotypes and resulting antibody-dependent enhancement (ADE) of infection are major concerns that have limited the development of effective vaccine against DENV. Therefore, there has been a significant emphasis on the development of antiviral drugs against dengue. This review article describes the rescue effects of some of the small molecule inhibitors to viral/host factors associated with DENV pathogenesis."

Journal • Dengue Fever • Infectious Disease • CXCR3

Discovery of Pyrano[2,3-c]pyrazole Derivatives as Novel Potential Human Coronavirus Inhibitors: Design, Synthesis, In Silico, In Vitro, and ADME Studies. (PubMed, Pharmaceuticals (Basel)) - "Likewise, when assessed to the positive control tipranavir (88.6%), the inhibitory efficiency of compounds 6, 7, 14, and 18 versus the SARS-CoV2 Mpro provided high percentages of 80.4%, 73.1%, 81.4% and up to 84.5%, respectively. In silico studies were performed to investigate further the biological activity and the target compounds' physical and chemical features, including molecular dynamic (MD) simulations, protein-ligand docking, ADME studies, and density functional theory (DFT) calculations. These inquiries demonstrated that this series of metabolically stable pyranopyrazoles and their annulated systems are effective human coronavirus inhibitors that inhibit the viral Mpro protein and may have emerged as a novel COVID-19 curative option."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Conformational diversity and protein-protein interfaces in drug repurposing in Ras signaling pathway. (PubMed, Sci Rep) - "The results suggest that HIV protease inhibitors tipranavir, indinavir, and saquinavir may bind to EGFR and ERBB3/HER3 interface. Additionally, a drug used in Alzheimer's disease can bind to RAF1 and BRAF interface. Hence, we propose a methodology to find drugs to be potentially used for cancer using a dataset of structurally similar protein-protein interface clusters rather than pockets in a systematic way."

Journal • Alzheimer's Disease • CNS Disorders • Human Immunodeficiency Virus • Infectious Disease • Oncology • BRAF • EGFR • ERBB3 • HER-2

Targeting PRSS23 with tipranavir induces gastric cancer stem cell apoptosis and inhibits growth of gastric cancer via the MKK3/p38 MAPK-IL24 pathway. (PubMed, Acta Pharmacol Sin) - "In contrast, combined treatment with 5-FU plus cisplatin did not affect the tumor growth but causing significant weight loss...In addition, tipranavir was found to kill other types of cancer cell lines and drug-resistant cell lines. Collectively, this study demonstrates that by targeting both GCSCs and GC cells, tipranavir is a promising anti-cancer drug, and the clinical development of tipranavir or other drugs specifically targeting the PRSS23/MKK3/p38MAPK-IL24 mitochondrial apoptotic pathway may offer an effective approach to combat gastric and other cancers."

Cancer stem • Journal • Gastric Cancer • Gastrointestinal Cancer • Human Immunodeficiency Virus • Infectious Disease • Oncology • Solid Tumor • MAP2K3 • PRSS23

Pharmacokinetics of Antiretroviral Drugs in Older People Living with HIV: A Systematic Review. (PubMed, Clin Pharmacokinet) - "Exposure to DRV increases modestly with age, while exposure to BIC, DOR and RAL appears to be unaffected by age. As the available evidence to confirm a potential effect of aging on ARV pharmacokinetics is limited, further studies are necessary."

Clinical • PK/PD data • Review • Human Immunodeficiency Virus • Infectious Disease

Virtual screening identifies tipranavir as a SIRT1 inhibitor with anti-hepatocarcinoma effect. (PubMed, Future Med Chem) - "Furthermore, tipranavir was found to suppress tumorigenesis in a xenograft mouse model and decreased the expression of SIRT1 in vivo. Tipranavir holds desirable potential as a promising therapeutic agent against hepatoma."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Liver Cancer • Oncology • Solid Tumor

Vitamin E TPGS-Based Nanomedicine, Nanotheranostics, and Targeted Drug Delivery: Past, Present, and Future. (PubMed, Pharmaceutics) - "Since then, four drugs with TPGS in their formulation have been approved for sale in the United States and Europe including ibuprofen, tipranavir, amprenavir, and tocophersolan...Docetaxel, paclitaxel, and doxorubicin are examples of poorly bioavailable therapeutic agents; hence, much effort is applied for developing TPGS-based nanomedicine, nanotheranostics, and targeted drug delivery systems to increase circulation time and promote the reticular endothelial escape of these drug delivery systems...However, various randomized or human clinical trials have been underway for TPGS-based drug delivery systems for multiple diseases such as pneumonia, malaria, ocular disease, keratoconus, etc. In this review, we have emphasized in detail the review of the nanotheranostics and targeted drug delivery approaches premised on TPGS. In addition, we have covered various therapeutic systems involving TPGS and its analogs with special references to its patent and clinical trials."

Journal • Review • Infectious Disease • Malaria • Oncology • Ophthalmology • Pneumonia • Respiratory Diseases

Discovery of Novel HIV Protease Inhibitors Using Modern Computational Techniques. (PubMed, Int J Mol Sci) - "The 10 FDA-approved HIV PIs (saquinavir, lopinavir, ritonavir, amprenavir, fosamprenavir, atazanavir, nelfinavir, darunavir, tipranavir and indinavir) were used as reference. HPS/002 and HPS/004 have been found to be most promising in terms of IC/percent inhibition (90.15%) of HIV-1 PR, in addition to their drug metabolism and safety profile. These hit candidates should be investigated further as possible HIV-1 PIs with improved efficacy and low toxicity through in vitro experiments and clinical trial investigations."

Journal • Human Immunodeficiency Virus • Immunology • Infectious Disease

In silico identification of potential inhibitors of vital monkeypox virus proteins from FDA approved drugs. (PubMed, Mol Divers) - "We identified four potential inhibitors namely, Tipranavir, Cefiderocol, Doxorubicin, and Dolutegravir as candidates for repurposing against monkeypox virus from a library of US FDA approved antiviral and antibiotic drugs using molecular docking and molecular dynamics simulations. The main goal of this in silico study is to identify potential inhibitors against monkeypox virus proteins that can be further experimentally validated for the discovery of novel therapeutic agents against monkeypox disease."

FDA event • Journal • Infectious Disease

Anticoagulants as Potential SARS-CoV-2 M Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies. (PubMed, Int J Mol Sci) - "Idraparinux, fondaparinux, eptifibatide, heparin, and ticagrelor demonstrated the highest binding affinities towards SARS-CoV-2 M. A molecular dynamics study at 200 ns was also carried out for the most promising anticoagulants to provide insights into the dynamic and thermodynamic properties of promising compounds...Interestingly, promising SARS-CoV-2 M inhibitory potential was attained for fondaparinux sodium with an IC value of 2.36 µM, surpassing the reference tipranavir (IC = 7.38 µM) by more than three-fold. Furthermore, highly eligible SARS-CoV-2 M inhibitory potential was attained for dabigatran with an IC value of 10.59 µM. Finally, an SAR was discussed, counting on the findings of both in vitro and in silico approaches."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Chemoinformatic Design and Profiling of Derivatives of Dasabuvir, Efavirenz, and Tipranavir as Potential Inhibitors of Zika Virus RNA-Dependent RNA Polymerase and Methyltransferase. (PubMed, ACS Omega) - "These compounds are potent inhibitors of N-7 and 2'-methylation activities of ZIKV methyltransferase and/or RNA synthesis through interactions with amino acid residues in the priming loop/"N-pocket" in the virus RdRP. Synthesis of these compounds and wet laboratory validation against ZIKV are recommended."

Journal • Hepatology • Infectious Disease • Oncology • CYP1A2 • CYP2C19 • CYP2C9

Molecular dynamics and docking studies on potentially active natural phytochemicals for targeting SARS-CoV-2 main protease. (PubMed, J Biomol Struct Dyn) - "From these screening we identified that Aegelinosides B leads the list with a high LibDock value of 142.50 (binding energy: -8.54 kcal/mol), which is better than several popular reference compounds namely, Tipranavir (LibDock score, 141.50), Saquinavir (125.34), Zopicole (122.9), Pirenepine (122.70), (115.37), Metixene (109.18), Oxiconazole Pimozide (138.00) and Rimonabant (91.88). Detailed analysis for structural stability (RMSD), Cα fluctuations (RMSF), intermolecular hydrogen bond interactions, effect of solvent accessibility (SASA) and compactness (Rg) factors were performed for the best six compounds and it is found that they are very stable and exhibit folding behavior. Apart from the docking and MD tests, through further drug-likeness and toxicity tests, three compounds, such as, Aegelinosides B, Epicatechin, and Feruloyltyramine (LibDock scores, respectively, 142.50, 124.33 and 129.06) can be suggested for fighting SARS-CoV-2.Communicated by Ramaswamy H. Sarma."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Design, synthesis and in silico screening of benzoxazole-thiazolidinone hybrids as potential inhibitors of SARS-CoV-2 proteases. (PubMed, RSC Adv) - "MD simulations demonstrated that the reference drug Tipranavir relocated to the thumb region of the protease whereas BT27 remained in the active site of PLp stabilized by 2 hydrogen bonds, while MBT9 relocated to the BL2 loop of the palm region...A four-step synthetic procedure was employed to synthesize the B-T hybrids starting from ammonium thiocyanate. The short-listed compounds in the case of 3CLp were synthesized and characterized using IR, NMR, and HRMS spectroscopic techniques."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Drug resistance pattern among ART-naive clients attending an HIV testing and counseling center in Dhaka, Bangladesh. (PubMed, J Med Virol) - "The drug resistance algorithm showed that all samples were fully resistant to tipranavir/ritonavir (TPV/r) drug except for one intermediate resistance...The drug resistance algorithm showed that all samples were fully resistant to tipranavir/ritonavir (TPV/r) drug except for one intermediate resistance. Despite the small sample size, our understanding from this study warrants an ART policy with a DRM monitoring system for the country."

Journal • Human Immunodeficiency Virus • Infectious Disease

Oral administration of tipranavir with long-chain triglyceride results in moderate intestinal lymph targeting but no efficient delivery to HIV-1 reservoir in mesenteric lymph nodes. (PubMed, Int J Pharm) - "Thus, LCT-based formulation approach alone was not sufficient for effective delivery of TPV to MLNs. Future efforts should be directed to a combined highly lipophilic prodrugs/lipid-based formulation approach to target TPV, other PIs and potentially other classes of antiretroviral agents to viral reservoirs within the mesenteric lymphatic system."

Journal • Human Immunodeficiency Virus • Infectious Disease

Multidomain drug delivery systems of β-casein micelles for the local oral co-administration of antiretroviral combinations. (PubMed, J Colloid Interface Sci) - "To simplify administration fixed-dose combinationshave been introduced, however, oral anti-HIV therapy still struggles with low oral bioavailability of many ARVs.This work investigated the co-encapsulation of two clinically relevant ARV combinations,tipranavir (TPV):efavirenz (EFV) anddarunavir (DRV):efavirenz (EFV):ritonavir (RTV),within the core of β-casein (bCN) micelles...At intestinal pH, the coating polymer dissolved and released the nanocarriers and content. Overall, our results confirm the promise of this flexible and modular technology platform for oral delivery of fixed dose combinations."

Journal • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammatory Arthritis • Novel Coronavirus Disease • Respiratory Diseases

In silico prediction of SARS-CoV-2 main protease and polymerase inhibitors: 3D-Pharmacophore modelling. (PubMed, J Biomol Struct Dyn) - "The present study used HEX and AutoDock Vina softwares to predict the affinity of about 100 medicinal structures toward the active site of 3-chymotrypsin-like protease (3Clpro) and RNA-dependent RNA polymerase (RdRp), separately...In addition to compound 45, tipranavir (28) and atazanavir (26) as FDA-approved HIV protease inhibitors were tightly interacted with the active site of SARS-CoV-2 main protease as well. Based on pharmacophore modelling, a good structural pattern for potent candidates against SARS-CoV-2 main enzymes is suggested. Re-tasking or taking inspiration from the structures of tegobuvir and tipranavir can be a proper approach toward coping with the COVID-19 in the shortest possible time and at the lowest cost."

Journal • Hepatitis C Virus • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents. (PubMed, Commun Biol) - "Our results indicate that boceprevir, ombitasvir, paritaprevir, tipranavir, ivermectin, and micafungin exhibited inhibitory effect towards 3CLpro enzymatic activity. The 100 ns molecular dynamics simulation studies showed that ivermectin may require homodimeric form of 3CLpro enzyme for its inhibitory activity. In summary, these molecules could be useful to develop highly specific therapeutically viable drugs to inhibit the SARS-CoV-2 replication either alone or in combination with drugs specific for other SARS-CoV-2 viral targets."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

"Als iemand te sexy is @Elodius, dan moet die juist meer op TV komen. #wewantpetra" (@fog_rock)

A revision of European species of the genus Tetrastichus Haliday (Hymenoptera: Eulophidae) using integrative taxonomy. (PubMed, Biodivers Data J) - "n., T. elodiussp...Hosts are known for 27 of the species and they are gregarious, koinobiont endoparasitoids on a wide range of immature stages of holometabolous insects and appear to be very host specific. The first host record for Lepidoptera (Tineidae) in Europe is included."

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